The goal of this project is to identify, isolate and characterize the thyroid-stimulating factor of trophoblastic origin that is responsible for thyroid hyperfunction in patients with trophoblastic tumors. It has been suggested by others that hCG has intrinsic thyrotropic activity and is the thyroid stimulator of molar pregnancy. This project's data support the hypothesis that molar hCG is different from molar TSH and that hCG is not the thyroid stimulator associated with molar pregnancy. Recent studies have suggested that certain modified forms of hCG have a higher affinity for binding to TSH receptors in thyroid than normal hCG itself does. Present studies are, therefore, directed at the selective modification of hCG subunits, the recombination of modified subunits and an assessment of the thyrotropic and gonadotropic activities of such molecules. Studies are also in progress to characterize the variants of hCG and its subunits that are excreted in normal pregnancy urine and in the urine of patients with trophoblastic tumors in an attempt to identify those that are unique to molar pregnancy.